One of the major clinical problems in diseases of Felidae is associated with respiratory tract infections. The great majority of these cases are caused by either feline herpesvirus 1 (FHV) or feline calicivirus.
FHV is the causative agent of feline viral rhinotracheitis in cats. In kittens, FHV infection can generalize resulting in mortality rates of up to 50%. The disease is common and is found world-wide and is characterized by sneezing, depression, and ocular and nasal discharge.
The FHV is a member of the family Herpes-viridae, subfamily .alpha.-herpesvirus. The genome is about 126 kbp in length and is composed of a unique long (U.sub.L) region of about 99 kbp and a short region of 27 kbp comprising an unique short (U.sub.s) region of about 9 kbp flanked by inverted repeats of about 8 kbp (Grail et al., Arch. Virol. 116, 209-220, 1991).
Because of the prevalence and seriousness of FHV infection feline viral rhinotracheitis vaccines comprising modified live or killed FHV have been developed and have resulted in a successful reduction of the incidence of the disease.
In addition to FHV infection, cats are also susceptible to infection by various other pathogens, such as feline leukemia virus (FeLV), feline calicivirus, feline immunodeficiency virus (FIV), feline coronavirus and feline Chlamydia. At present, in general, cats can be protected against infection by these pathogenic micro-organisms with live or inactivated vaccines or by vaccines derived from subunits of the relevant pathogens.
However, these types of vaccines may suffer from a number of drawbacks. Using attenuated live vaccines always involves the risk of inoculating animals with inadequately attenuated pathogenic micro-organisms. In addition the attenuated pathogens may revert to a virulent state resulting in disease of the inoculated animals and the possible spread of the pathogen to other animals.
Inactivated vaccines generally induce only a low level of immunity, requiring repeated immunizations. Furthermore, the neutralization inducing antigenic determinants of the pathogens may become altered by the inactivation treatment, decreasing the protective potency of the vaccine.
Moreover, a problem with combined live viral vaccines is the mutual influence of the antigenic components resulting in a decrease of the potency of one or more of the constituting components.
A recombinant or naturally derived subunit vaccine also displays a number of disadvantages. First, a polypeptide subunit presented to the immune system as a non-replicating structure often does not elicit long-lasting immunity requiring also the presence of an adjuvant. Secondly, a presentation as a replicating structure can elicit immunity more efficiently than can a presentation as a subunit structure.
Furthermore, with currently administered live attenuated or inactivated FHV vaccines it is not possible to determine whether a specific animal is a carrier of an FHV field virus or whether the animal was vaccinated. Hence, it is important to be able to identify animals vaccinated with an FHV vaccine or infected with a field virus so as to be able to take appropriate measures to reduce spreading of a virulent field virus.
It is an object of the present invention to provide an FHV mutant which can be used not only for the preparation of a vaccine against feline viral rhinotracheitis but also against other infectious diseases of Felidae, which obviates any potential risk associated with the use of a live attenuated pathogen as a vaccine, which stimulates both the humoral and cellular immune system in a potent way without the explicit need of an adjuvant and which offers the possibility of a multivalent vaccine without the risk of adverse mutual interference of different antigenic components.
An other object of the present invention is to provide an FHV vaccine virus which is distinguishable from any field strain or any other FHV vaccine virus.